CA2986432A1 - In vitro cell culture methods for beta-thalassemia using activin type ii receptor ligand traps - Google Patents
In vitro cell culture methods for beta-thalassemia using activin type ii receptor ligand trapsInfo
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- CA2986432A1 CA2986432A1 CA2986432A CA2986432A CA2986432A1 CA 2986432 A1 CA2986432 A1 CA 2986432A1 CA 2986432 A CA2986432 A CA 2986432A CA 2986432 A CA2986432 A CA 2986432A CA 2986432 A1 CA2986432 A1 CA 2986432A1
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- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
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- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
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- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0641—Erythrocytes
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- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
- C12Q1/025—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/4833—Physical analysis of biological material of solid biological material, e.g. tissue samples, cell cultures
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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- A—HUMAN NECESSITIES
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- A61K39/00—Medicinal preparations containing antigens or antibodies
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- A61K2039/515—Animal cells
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
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- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/10—Growth factors
- C12N2501/16—Activin; Inhibin; Mullerian inhibiting substance
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Applications Claiming Priority (5)
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| US201562164367P | 2015-05-20 | 2015-05-20 | |
| US62/164,367 | 2015-05-20 | ||
| US201662320032P | 2016-04-08 | 2016-04-08 | |
| US62/320,032 | 2016-04-08 | ||
| PCT/US2016/033187 WO2016187378A1 (en) | 2015-05-20 | 2016-05-19 | In vitro cell culture methods for beta-thalassemia using activin type ii receptor ligand traps |
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| CA2986432A1 true CA2986432A1 (en) | 2016-11-24 |
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| CA2986432A Pending CA2986432A1 (en) | 2015-05-20 | 2016-05-19 | In vitro cell culture methods for beta-thalassemia using activin type ii receptor ligand traps |
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| NZ707477A (en) | 2012-11-02 | 2019-09-27 | Celgene Corp | Activin-actrii antagonists and uses for treating bone and other disorders |
| MA41052A (fr) | 2014-10-09 | 2017-08-15 | Celgene Corp | Traitement d'une maladie cardiovasculaire à l'aide de pièges de ligands d'actrii |
| JP2018501307A (ja) | 2014-12-03 | 2018-01-18 | セルジーン コーポレイション | アクチビン−ＡｃｔＲＩＩアンタゴニスト及び貧血を治療するための使用 |
| WO2016187378A1 (en) | 2015-05-20 | 2016-11-24 | Celgene Corporation | In vitro cell culture methods for beta-thalassemia using activin type ii receptor ligand traps |
| US11123430B2 (en) | 2015-11-04 | 2021-09-21 | Acceleron Pharma Inc. | Methods for increasing red blood cell levels and treating ineffective erythropoiesis |
| WO2018089715A1 (en) | 2016-11-10 | 2018-05-17 | Keros Therapeutics, Inc. | Activin receptor type iia variants and methods of use thereof |
| EP3567096B1 (en) * | 2017-01-06 | 2024-05-29 | Evident Corporation | Cell observation system |
| CA3082146A1 (en) * | 2017-11-09 | 2019-05-16 | Keros Therapeutics, Inc. | Activin receptor type iia variants and methods of use thereof |
| KR20200109330A (ko) | 2018-01-12 | 2020-09-22 | 케로스 테라퓨틱스, 인크. | 액티빈 수용체 유형 iib 변이체 및 그의 사용 방법 |
| CA3098679A1 (en) * | 2018-05-09 | 2019-11-14 | Keros Therapeutics, Inc. | Activin receptor type iia variants and methods of use thereof |
| JP7388679B2 (ja) * | 2019-05-28 | 2023-11-29 | 学校法人 東洋大学 | 熱中症マーカー及びその利用 |
| IL296394A (en) * | 2020-03-20 | 2022-11-01 | Keros Therapeutics Inc | Type ii activin receptor chimeras and methods of using them |
| EP4121088A4 (en) | 2020-03-20 | 2024-07-03 | Keros Therapeutics, Inc. | Methods of using activin receptor type iib variants |
| KR20230017193A (ko) * | 2020-04-28 | 2023-02-03 | 악셀레론 파마 인코포레이티드 | Actrii 단백질 및 후모세혈관 폐 고혈압 치료에서의 용도 |
| MX2022016237A (es) * | 2020-06-23 | 2023-03-08 | Acceleron Pharma Inc | Proteinas actrii para el tratamiento de la hipertension arterial pulmonar (hap). |
| US12186370B1 (en) | 2020-11-05 | 2025-01-07 | Celgene Corporation | ACTRIIB ligand trap compositions and uses thereof |
| EP4240399A4 (en) * | 2020-11-06 | 2024-10-09 | Acceleron Pharma Inc. | FORMULATIONS WITH ACTRII POLYPEPTIDE VARIANTS |
Family Cites Families (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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| EP1356075A4 (en) | 2000-10-16 | 2005-04-13 | Compound Therapeutics Inc | PROTEIN EQUIPMENT FOR ANTIBODY MIMETICS AND OTHER TIE PROTEINS |
| US7754208B2 (en) | 2001-01-17 | 2010-07-13 | Trubion Pharmaceuticals, Inc. | Binding domain-immunoglobulin fusion proteins |
| US20030133939A1 (en) | 2001-01-17 | 2003-07-17 | Genecraft, Inc. | Binding domain-immunoglobulin fusion proteins |
| ATE472609T1 (de) | 2001-04-26 | 2010-07-15 | Amgen Mountain View Inc | Kombinatorische bibliotheken von monomerdomänen |
| AU2005266875B2 (en) | 2004-07-23 | 2012-07-26 | Acceleron Pharma Inc. | ActRII receptor polypeptides, methods and compositions |
| JP2008520207A (ja) | 2004-11-16 | 2008-06-19 | アヴィディア リサーチ インスティテュート | タンパク質骨格およびその使用 |
| CN105001320A (zh) | 2005-11-23 | 2015-10-28 | 阿塞勒隆制药公司 | Activin-ActRIIa拮抗剂及其促进骨骼生长的应用 |
| US20100028332A1 (en) | 2006-12-18 | 2010-02-04 | Acceleron Pharma Inc. | Antagonists of actriib and uses for increasing red blood cell levels |
| US8895016B2 (en) | 2006-12-18 | 2014-11-25 | Acceleron Pharma, Inc. | Antagonists of activin-actriia and uses for increasing red blood cell levels |
| AU2007334333B2 (en) | 2006-12-18 | 2013-05-30 | Acceleron Pharma Inc. | Activin-ActRII antagonists and uses for increasing red blood cell levels |
| CN101835485B (zh) | 2007-02-01 | 2016-10-26 | 阿塞勒隆制药公司 | 活化素-actriia拮抗剂及在治疗或预防乳腺癌中的用途 |
| TW201940502A (zh) | 2007-02-02 | 2019-10-16 | 美商艾瑟勒朗法瑪公司 | 衍生自ＡｃｔＲＩＩＢ的變體與其用途 |
| JP5574711B2 (ja) | 2007-02-09 | 2014-08-20 | アクセルロン ファーマ， インコーポレイテッド | 癌患者における骨成長を促進するためのアクチビン−ａｃｔｒｉｉａアンタゴニストおよびその使用 |
| EP3243524A1 (en) | 2007-09-18 | 2017-11-15 | Acceleron Pharma Inc. | Activin-actriia antagonists and uses for decreasing or inhibiting fsh secretion |
| EP2315602A4 (en) | 2008-06-26 | 2011-11-02 | Acceleron Pharma Inc | METHOD OF DOSING AN ACTRIIB ANTAGONIST AND MONITORING TREATED PATIENTS |
| WO2010019261A1 (en) | 2008-08-14 | 2010-02-18 | Acceleron Pharma Inc. | Use of gdf traps to increase red blood cell levels |
| US8216997B2 (en) | 2008-08-14 | 2012-07-10 | Acceleron Pharma, Inc. | Methods for increasing red blood cell levels and treating anemia using a combination of GDF traps and erythropoietin receptor activators |
| EP2387412A4 (en) | 2009-01-13 | 2013-04-03 | Acceleron Pharma Inc | PROCESS FOR INCREASING THE ADIPONECTIN MIRROR |
| US8178488B2 (en) | 2009-06-08 | 2012-05-15 | Acceleron Pharma, Inc. | Methods for increasing thermogenic adipocytes |
| BRPI1010704B1 (pt) | 2009-06-12 | 2021-12-14 | Acceleron Pharma Inc | Polipeptídeo recombinante, proteína de fusão recombinante, preparação farmacêutica e uso da mesma |
| CN105535938B (zh) * | 2009-08-13 | 2022-04-26 | 阿塞勒隆制药公司 | Gdf捕获物和促红细胞生成素受体激活剂联合应用以增加红细胞水平 |
| KR20210029836A (ko) | 2009-09-09 | 2021-03-16 | 악셀레론 파마 인코포레이티드 | ＡｃｔＲＩＩｂ 길항제들와 이의 투약 및 용도 |
| ES2869864T3 (es) | 2009-11-03 | 2021-10-26 | Acceleron Pharma Inc | Procedimientos para el tratamiento de la enfermedad del hígado graso |
| JP6267425B2 (ja) | 2009-11-17 | 2018-01-24 | アクセルロン ファーマ， インコーポレイテッド | 筋ジストロフィー治療のためのユートロフィン誘導に関するａｃｔｒｉｉｂタンパク質およびその改変体およびその使用 |
| CN107837390A (zh) | 2011-10-17 | 2018-03-27 | 阿塞勒隆制药公司 | 用于治疗无效性红细胞生成的方法和组合物 |
| CN112933223A (zh) | 2012-10-24 | 2021-06-11 | 细胞基因公司 | 用于治疗贫血的方法 |
| CN113604550A (zh) | 2012-10-24 | 2021-11-05 | 细胞基因公司 | 用于治疗贫血症的生物标志物 |
| NZ707477A (en) | 2012-11-02 | 2019-09-27 | Celgene Corp | Activin-actrii antagonists and uses for treating bone and other disorders |
| BR112016024319B1 (pt) | 2014-04-18 | 2024-01-23 | Acceleron Pharma Inc | USO DE UMA COMPOSIÇÃO COMPREENDENDO UM ANTAGONISTA DE ActRII PARA A FABRICAÇÃO DE UM MEDICAMENTO PARA TRATAR OU PREVINIR UMA COMPLICAÇÃO DE ANEMIA FALCIFORME |
| AP2017009674A0 (en) | 2014-06-13 | 2017-01-31 | Acceleron Pharma Inc | Methods and compositions for treating ulcers |
| MA41052A (fr) | 2014-10-09 | 2017-08-15 | Celgene Corp | Traitement d'une maladie cardiovasculaire à l'aide de pièges de ligands d'actrii |
| JP2018501307A (ja) | 2014-12-03 | 2018-01-18 | セルジーン コーポレイション | アクチビン−ＡｃｔＲＩＩアンタゴニスト及び貧血を治療するための使用 |
| MA41119A (fr) | 2014-12-03 | 2017-10-10 | Acceleron Pharma Inc | Méthodes de traitement de syndromes myélodysplasiques et d'anémie sidéroblastique |
| KR102640198B1 (ko) | 2015-05-13 | 2024-02-23 | 셀진 코포레이션 | Actrii 리간드 트랩을 사용한 베타-탈라세미아의 치료 |
| WO2016187378A1 (en) | 2015-05-20 | 2016-11-24 | Celgene Corporation | In vitro cell culture methods for beta-thalassemia using activin type ii receptor ligand traps |
| US11123430B2 (en) | 2015-11-04 | 2021-09-21 | Acceleron Pharma Inc. | Methods for increasing red blood cell levels and treating ineffective erythropoiesis |
| WO2017091706A1 (en) | 2015-11-23 | 2017-06-01 | Acceleron Pharma Inc. | Methods for treating eye disorders |
| RS62011B1 (sr) | 2016-07-15 | 2021-07-30 | Acceleron Pharma Inc | Kompozicije koje sadrže polipeptide actriia za upotrebu u lečenju plućne hipertenzije |
| RS65735B1 (sr) | 2016-07-27 | 2024-08-30 | Acceleron Pharma Inc | Kompozicije za upotrebu u lečenju mijelofibroze |
| JP7496686B2 (ja) | 2017-06-14 | 2024-06-07 | セルジーン コーポレイション | 骨髄増殖性腫瘍関連骨髄線維症及び貧血を治療するための方法 |
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2016
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- 2016-05-19 HK HK18111575.0A patent/HK1252174A1/zh unknown
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| EP3298034A4 (en) | 2019-02-13 |
| CN108350057A (zh) | 2018-07-31 |
| EP3298034A1 (en) | 2018-03-28 |
| JP2022023072A (ja) | 2022-02-07 |
| US10548976B2 (en) | 2020-02-04 |
| US20180161426A1 (en) | 2018-06-14 |
| WO2016187378A1 (en) | 2016-11-24 |
| MA42160A (fr) | 2018-03-28 |
| HK1252174A1 (zh) | 2019-05-17 |
| EP4190805A3 (en) | 2023-08-16 |
| US20200101157A1 (en) | 2020-04-02 |
| EP4190805A2 (en) | 2023-06-07 |
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